Carbenoid pathways in copper-catalyzed intramolecular cyclopropanations of phenyliodonium ylides

Article abstract of DOI:10.1002/1522-2675(20010516)84:5<1093::AID-HLCA1093>3.0.CO;2-T

The enantioselectivity of the copper-catalyzed intramolecular cyclopropanation of allyl diazomalonates and the corresponding phenyliodonium ylides was investigated with a series of chiral, non-racemic ligands. The reaction of 6b in the presence of the bis[dihydrooxazole] ligand Xa in refluxing 1,2-dichloroethane proceeded to 8b with an enantiomer excess (ee) of up to 72% under optimized conditions. In contrast, 8b resulting from reaction of ylide 7b with the same ligand, but in CH₂Cl₂ at 0°, had an ee of only 30%. With other ligands, diazomalonate 6b reacted with a lower enantioselectivity than ylide 7b, however. The intramolecular cyclopropanation of the acetoacetate-derived phenyliodonium ylide 15b afforded 16b with 68% ee with ligand Xa, but the corresponding diazo compound was unreactive when exposed to chiral copper catalysts. The observation of asymmetric induction in the Cu-catalyzed reactions of the ylides 7 and 15 is consistent with a carbenoid mechanism however, the discrepancy of the enantioselectivities observed between diazomalonate 6b and ylide 7b suggests a competing unselective pathway for cyclopropanation outside of the coordination sphere of copper.

Full text of DOI:10.1002/1522-2675(20010516)84:5<1093::AID-HLCA1093>3.0.CO;2-T

Helvetica Chimica Acta ± Vol. 84 (2001)
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Carbenoid Pathways in Copper-Catalyzed Intramolecular
Cyclopropanations of Phenyliodonium Ylides
by Paul Müller* and Christelle BoleÂa
Department of Organic Chemistry, University of Geneva 30, Quai Ernest Ansermet, CH-1211 Geneva 4
The enantioselectivity of the copper-catalyzed intramolecular cyclopropanation of allyl diazomalonates
and the corresponding phenyliodonium ylides was investigated with a series of chiral, non-racemic ligands. The
reaction of 6b in the presence of the bis[dihydrooxazole] ligand Xa in refluxing 1,2-dichloroethane proceeded to
8b with an enantiomer excess (ee) of up to 72% under optimized conditions. In contrast, 8b resulting from
reaction of ylide 7b with the same ligand, but in CH2Cl2 at 08, had an ee of only 30%. With other ligands,
diazomalonate 6b reacted with a lower enantioselectivity than ylide 7b, however. The intramolecular
cyclopropanation of the acetoacetate-derived phenyliodonium ylide 15b afforded 16b with 68% ee with ligand
Xa, but the corresponding diazo compound was unreactive when exposed to chiral copper catalysts. The
observation of asymmetric induction in the Cu-catalyzed reactions of the ylides 7 and 15 is consistent with a
carbenoid mechanism; however, the discrepancy of the enantioselectivities observed between diazomalonate 6b
and ylide 7b suggests a competing unselective pathway for cyclopropanation outside of the coordination sphere
of copper.
Introduction. ± The photochemical [1], thermal [2], or transition-metal-catalyzed
[1][3][4] decomposition of phenyliodonium ylides [5] affords products typical for
carbene or metal carbenoid intermediates. The mechanism of these reactions is,
however, controversial. Carbene or carbenoid pathways have often been proposed or
assumed, but experimental evidence in support of these hypotheses is scarce. Some
years ago, we have investigated the decomposition of some diazo compounds and the
corresponding phenyliodonium ylides in the presence of [RhII(carboxylato)] catalysts.
Both precursors afforded the same selectivities in the intermolecular cyclopropanation
of substituted styrenes and in the intramolecular competition for cyclopropanation vs.
CH insertion. In addition, identical enantioselectivities resulted when the intra-
molecular CH insertion of a diazoacetoacetate and the corresponding phenyliodonium
ylide was carried out in the presence of Ikegamiꢀs chiral [RhII(carboxylato)] catalyst
[6]. These results are consistent with a carbenoid mechanism.
However, the majority of the synthetically useful reactions with phenyliodonium
ylides have been carried out under Cu-catalysis, and for Cu-catalysts the mechanism is
not established. Moriarty et al. investigated the intramolecular cyclopropanation of
ylide 1 to the tricyclic ketone 4 in the presence of [CuCl] (Scheme 1) [7]: the reaction
proceeded in yields of 76 to 90%; surprisingly, it also occurred in the absence of
catalyst, albeit in lower yield. The authors proposed a mechanism in which the
electrophilic iodonium center attacks the CˆC bond to afford a carbenium ion 2,
which, subsequently, undergoes transannular alkylation to yield 3. Reductive elimi-
nation of PhI from 3 finally produces the cyclopropane 4. The catalytic effect of CuI, in
turn, was ascribed to electron transfer. A carbene mechanism was specifically ruled out.

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Helvetica Chimica Acta ± Vol. 84 (2001)
Scheme 1
According to the mechanism of Moriarty et al., the reaction does not take place in
the coordination sphere of the metal, and, therefore, no asymmetric induction is to be
expected if the decomposition of the iodonium ylide is effected by a chiral catalyst.
Indeed, no enantioselective reactions of such ylides in conjunction with chiral, non-
racemic Cu-catalysts have yet been reported in the literature. In this communication,
we present the first observation of enantioselective intramolecular cyclopropanations
with phenyliodonium ylides under Cu-catalysis. Some of the results have been
published in preliminary form [8].
Results and Discussion. ± Two known types of Cu-catalyzed intramolecular
cyclopropanations were selected from the literature for this investigation, starting from
diazomalonates and diazoacetoacetates, and/or the corresponding phenyliodonium
ylides, respectively, as precursors. Our approach consisted in optimizing first the
enantioselectivity of the diazo decomposition by screening a large number of Cu-
catalysts and varying the reaction conditions. Subsequently, the corresponding phenyl-
iodonium ylides were to be reacted under the same conditions. The observation of
enantioselectivity upon reaction of the ylides would rule out the mechanism of
Moriarty et al. Since the carbenoid nature of the Cu-catalyzed diazo decomposition is
well-established [9], identical enantioselectivities for cyclopropanations, starting from
the diazo compounds and from the corresponding ylides, respectively, under identical
conditions, was expected to provide strong evidence in favor of a carbenoid pathway in
Cu-catalyzed cyclopropanations of phenyliodonium ylides.
Cu-Catalyzed Decomposition of Allyl tert-Butyl 2-(phenyliodonio)malonate (7b).
The Cu-catalyzed cyclopropanation of the allyl diazomalonates 6a,b has been
investigated by Koskinen et al. [10] with the objective to synthesize optically pure
aminocyclopropane-1-carboxylic acids. The cyclopropanation of 6b with [CuI-
{P(OEt)3}] required heating to >1058 overnight and provided 8b in 76% yield. The
reaction of 6a,b with [CuOTf] (Tf ˆ (trifluoromethyl)sulfonyl), and the chiral
bis[dihydrooxazole] ligand VI occurred in 1,2-dichloroethane (CH2Cl)2 already at 658
and afforded 8a,b in 72 ± 73% yield. Enantioselectivities of 11 and 32% ee were
obtained with the methyl ester 6a and with the tert-butyl ester 6b, respectively. No diazo
decomposition took place at lower temperatures, however. The low reactivity of

Helvetica Chimica Acta ± Vol. 84 (2001)
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diazomalonates in the presence of Cu-catalysts (and [RhII(carboxamidato)] catalysts is
notorious [11].
We have prepared 6b,c by diazo transfer from tert-butyl allyl malonate (5b) and
benzyl allyl malonate (5c), respectively according to the procedure of Koskinen et al. A
selection of chiral ligands (see I ± III and V± XV in the Fig.) in conjunction with 2%
(with respect to the diazo compound) of [Cu(OTf)2] in (CH2Cl)2 was then examined at
658. The ligands I and II are commercially available. Most of the other ligands and
catalyst XVI were synthesized according to literature procedures (see Exper. Part),
except III, IV, VIIc, IX, Xb, XI, XIIc, and XVb ± d, which were designed and
synthesized specifically for this investigation (see below). The results of the Cu-
catalyzed cyclopropanation in their presence are summarized in Table 1. All of the
ligands tested were sufficiently reactive to effect diazo decomposition at 658, although
the yields of cyclopropanation products were quite variable. Even tertiary amines such
as sparteine (I) or the piperidine derivative II, which are not generally applied in diazo
decompositions, were found effective. The enantioselectivities produced by the
catalysts varied enormously and in an unpredictable manner. For example, in the
bis[dihydrooxazole] series V± VII, increasing the bulk of the substituents from
isopropyl to tert-butyl resulted in an increase in enantioselectivity from 28 to 40% with
6b, but with the Ph-substituted bis[dihydrooxazole] VI, the ee decreased to 12%. In
general, the enantioselectivity in the decomposition of tert-butyl malonate 6b was
higher than that of the benzyl malonate 6c, although there were exceptions (i.e. with
II). In addition, the decomposition of 6c required a slightly higher temperature than
the 808 required for 6b. The highest enantioselectivity (74% ee) was produced by the
binaphthalene-derived bis[dihydrooxazole] Xa. This enantioselectivity compares
favorably with the 32% ee reported by Koskinen et al. [10] with ligand V.
Further improvement of yield and enantioselectivity was attempted by optimization
of the reaction conditions with 6b and the most efficient ligand Xa (Table 2). Slow
addition of 6b within 16 h to the catalyst rather than at once had a detrimental effect on
the enantioselectivity of the reaction, which decreased from 74 to 29% ee, while the
yield increased from 21 to 52%. This is probably due to partial decomposition of the
catalyst owing to the high reaction temperature [12]. In agreement with this hypothesis,
the ee increased slightly to 74% when 6b was added at once to the solution containing
Scheme 2

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Helvetica Chimica Acta ± Vol. 84 (2001)
Figure. Catalysts and ligands

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1097
Table 1. Cu-Catalyzed Intramolecular Cyclopropanation of Diazomalonates 6a ± c
Diazo
compound
R
Ligand
(mol-%)
Solvent, Temp.
[8]
Product
Yield
[%]
ee
[%]
Ref., abs.
configuration
6a
6b
6b
6b
6b
6b
6b
6b
6b
6b
6b
6b
6b
6b
6b
6b
6b
6b
6b
6c
6c
6c
6c
6c
6c
6c
6c
6c
6c
6c
Me
V (5)
[CuI/P(OEt)3]
I (2)
II (5)
III (2)
IV (5)
V (5)
V (5)
VI (2)
VIIa (2)
VIIb (5)
VIIc (2)
VIIIa (2)
IX (2)
Xa (2)
Xb (2)
XI (2)
XIIc (2)
XVI (2)
I (5)
II (5)
VI (5)
(CH2Cl)2, 65
MeC6H5, 105
(CH2Cl)2, 65
(CH2Cl)2, 65
(CH2Cl)2, 65
(CH2Cl)2, 65
(CH2Cl)2, 65
(CH2Cl)2, 85
(CH2Cl)2, 65
(CH2Cl)2, 65
(CH2Cl)2, 65
(CH2Cl)2, 65
(CH2Cl)2, 65
(CH2Cl)2, 65
(CH2Cl)2, 65
(CH2Cl)2, 65
(CH2Cl)2, 65
(CH2Cl)2, 65
(CH2Cl)2, 65
(CH2Cl)2, 65
(CH2Cl)2, 80
(CH2Cl)2, 80
(CH2Cl)2, 80
(CH2Cl)2, 80
(CH2Cl)2, 80
(CH2Cl)2, 80
(CH2Cl)2, 80
(CH2Cl)2, 80
(CH2Cl)2, 80
(CH2Cl)2, 80
8a
8b
8b
8b
8b
8b
8b
8b
8b
8b
8b
8b
8b
8b
8b
8b
8b
8b
8b
8c
8c
8c
8c
8c
8c
8c
8c
8c
8c
8c
72
76
55
48
54
71
73
±
11
±
[10], (1R,5S)
[10]
tBu
tBu
22
11
00
00
32
15
12
28
40
35
38
05
74
22
22
02
25
04
15
13
15
12
10
00
04
13
01
42
tBu
tBu
tBu
tBu
[10] (1S,5S)
[10]
tBu
tBu
78
73
53
81
52
48
21
44
41
52
50
35
33
50
52
51
52
41
57
63
48
51
(1S,5S)
(1S,5S)
(1S,5S)
(1S,5S)
(1R,5R)
(1S,5S)
(1S,5S)
(1S,5S)
(1R,5R)
(1S,5S)
(1S,5S)
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
CH2Ph
CH2Ph
CH2Ph
CH2Ph
CH2Ph
CH2Ph
CH2Ph
CH2Ph
CH2Ph
CH2Ph
CH2Ph
VIIa (5)
VIIb (5)
VIIc (5)
IX (5)
Xa (5)
Xb (5)
XIIc (5)
XVI (5)
Table 2. Optimization of the Cyclopropanation with 6b and ligand Xaa)
Entry
Solventa)
Temp. [8]
Yield [%] of 8b
ee [%]
Comment
1
2
3
4
5
6
(CH2Cl)2
(CH2Cl)2
(CH2Cl)2
TFTb)
65
65
65
65
100
100
21
52
24
19
51
38
74
29
83
77
72
11
Addition of 6b at once
Addition of 6b within 16 h
Simultaneous addition of 6b and Xa, 16 h
Addition of 6b at once
Addition of 6b at once
TFTb)
Toluene
Addition of 6b at once
a) 2 mol-% of catalyst. b) TFTˆ trifluorotoluene ˆ (trifluoromethyl)benzene.
the catalyst, and it reached 83% when 6b and the catalyst were added simultaneously
within 16 h to the reaction mixture. A change of solvent from (CH2Cl)2 to
trifluorotoluene (TFT) had no significant effect, while a temperature increase from
65 to 1008 in TFT resulted in a significant increase in yield and only moderate loss of
enantioselectivity. Several RhII catalysts were also investigated for the purpose of

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Helvetica Chimica Acta ± Vol. 84 (2001)
comparison. Although the chemical yields of these reactions were satisfactory, the
enantioselectivities never exceeded 10% [13].
In the light of the disappointing enantioselectivities resulting from the diazo
decomposition of the benzyl ester 6c, work with this group was discontinued, and the
subsequent reactions were carried out only with the tert-butyl derivative. The
phenyliodonium ylide 7b was prepared by reaction of 5b with PhI(OAc)2 in MeOH
in the presence of KOH [5]. This reaction proved to be very delicate. The ylide was
unstable, and its formation was accompanied by substantial quantities of formal
carbene dimers, the structures of which were not further investigated. In addition,
transesterification of 5b to tert-butyl methyl malonate occurred under the conditions of
the reaction owing to ester exchange with the solvent. This secondary reaction could be
suppressed by replacing MeOH with MeCN as solvent. With this modified procedure,
the ylide 7b was obtained as a yellow oil in yields varying from 55 to 80%.
The cyclopropanation of 7b was effected with a selection of the catalysts used for
the diazo decomposition (Table 3). Reactions were carried out routinely in CH2Cl2 at
08, and some variations in the reaction conditions were studied with ligand VIIc. For
reasons of the instability of 7b, the cyclopropanations could not be carried out under
the conditions required for diazo decomposition, so that the enantioselectivities for 6b
and 7b with the same ligands are not directly comparable. Since the reactions with 7b
were effected at lower temperature than those of 6b, the enantioselectivities are
expected to be higher with 7b. This is true in some cases (i.e. with ligands VI and VIIc),
but in others (i.e. VIIa, VIIb, and Xa), the reverse trend results. The observation of
enantioselectivity (up to 45% ee in the cyclopropanation of 7b) indicates a reaction
mechanism occurring in close proximity to the chiral catalyst. However, the irregular
trends in the enantioselectivities upon reaction of diazomalonates and ylides show that
some other pathway for cyclopropanation of the ylide must be available.
Table 3. Cu-Catalyzed Intramolecular Cyclopropanation with Phenyliodonium Ylide 7b
Ligand
(mol-%)
Solvent
Temp [8]
Yield [%] of 8b
ee [%]
VI
(2)
(2)
(2)
(2)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
TFTa)
0
0
0
0
0
20
50
78
0
48
40
18
46
47
45
43
41
47
34
31
22
11
42
40
42
45
34
25
30
VIIa
VIIb
VIIc
VIIc
VIIc
VIIc
VIIc
VIIc
Xa
(4)
(2.4)
(2.4)
(2.4)
(2.4)
(2)
CH2Cl2
0
a) TFTˆ trifluorotoluene.
Intramolecular Cyclopropanation of Phenyliodonium Ylide 15a,b,d. In view of the
instability of ylide 7b, we turned our attention to the prostaglandin precursor 16, which
has been synthesized in the past by intramolecular cyclopropanation of the
diazoacetoacetates 14a [14] and 14c [15] and from the phenyliodonium ylide 15a [16]
(Scheme 3). The keto esters 13a,b,d were synthesized from (2E,4E)-deca-2,4-dienal (9)

Helvetica Chimica Acta ± Vol. 84 (2001)
1099
according to established procedures with some minor modifications. DIBAL Reduction
of aldehyde 9 afforded the known alcohol 10 [17][18], which was converted to the
labile bromide 11 with Br2/PPh3 [17]. Alkylation of 11 with the dianions of
acetoacetates 12a,b,d [19] afforded the keto esters 13a,b,d. Methyl ester 13a was
subjected to diazo transfer [20] to yield the diazoacetoacetate 14a. Reaction of 13a,b,d
with PhI(OAc)2 and KOH in MeOH, as described by Moriarty et al. [16], gave the
phenyliodonium ylides 15a,b,d. This latter transformation was much less problematic
than that of the malonate-derived ylide 7b. The ylides were isolated as yellow oils in
85 ± 87% crude yield and were used without further purification.
Scheme 3
The diazoesters 14a,c have been thermolyzed in refluxing benzene in the presence
of [Cu(acac)2] for 24 h [14] or in refluxing toluene (2 h) in the presence of copper
bronze [15] to give 16a and 16c in 63 and 50% yield, respectively (Table 4). We found
14a unreactive towards decomposition with the conventionally used [Cu-(bis[dihy-
drooxazole] catalysts. The camphor-derived Cu-catalyst IV [21] was more reactive
owing to the electron-attracting fluorinated side chain; IV effected diazo decompo-
sition of 14a in refluxing benzene to afford 16a in 45% yield. However, the product was
racemic. In contrast, ylide 15a reacted in CH2Cl2 at 08 with all of the catalysts to give 16a
in yields of 22 ± 63%. A selection of chiral ligands was screened; enantioselectivity was
modest and culminated at 42% ee. With the more hindered tert-butyl ester 15b, the ee
increased to 68%. However, with the still more crowded 2-methyl-1-(1-methylethyl)-
propyl ester 15d, the enantioselectivity deteriorated, except with ligand VIIIa, which

1100
Helvetica Chimica Acta ± Vol. 84 (2001)
Table 4. Intramolecular Cyclopropanation of 14 and 15
Diazo compound
or ylide
R
Catalyst or ligand
(mol-%)
Solvent, T [8]
Product
Yield [%]
ee [%]
Ref.
[14]
14a
14a
14c
15a
15a
15a
15a
15a
15a
15a
15a
15a
15a
15a
15a
15a
15a
15b
15b
15b
15b
15b
15b
15b
15b
15d
15d
15d
15d
15d
15d
15d
15d
Me
Me
Et
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
[Cu(acac)2]
IV (5)
Cu-bronze
[CuCl]
III (2)
IV (5)
C6H6, 80
C6H6, 80
16a
16a
16c
16a
16a
16a
16a
16a
16a
16a
16a
16a
16a
16a
16a
16a
16a
16c
16c
16c
16c
16c
16c
16c
16c
16d
16d
16d
16d
16d
16d
16d
16d
63
45
50
75
45
56
22
52
54
55
63
61
59
57
36
50
42
53
45
48
51
54
52
53
55
76
79
65
63
65
52
54
54
±
0
±
±
toluene, 110
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
CH2Cl2, 0
[15]
[16]
03
10
25
38
11
32
21
18
42
07
34
33
39
62
16
68
22
26
07
40
14
±
Xa (5)
Xb (5)
XIIa (2)
XIIb (2)
XIIc (2)
XIII (2)
XIV (2)
IX (5)
XVb (2)
XVc (2)
XVd (2)
VIIIa (2)
VIIIb (2)
Xa (2)
Me
tBu
tBu
tBu
tBu
Xb (2)
XI (2)
tBu
tBu
XIIb (2)
XIV (2)
XVd (2)
[Rh2(OAc)4]
VIIIa (2)
Xa (2)
Xb (2)
XI (2)
XIIv (2)
XIV (2)
XVb (2)
tBu
tBu
iPr2CH
iPr2CH
iPr2CH
iPr2CH
iPr2CH
iPr2CH
iPr2CH
iPr2CH
52
02
12
07
08
10
10
yielded 52% ee. The ylides reacted also with RhII catalysts; however, the enantiose-
lectivities in these latter reactions were unsatisfactory with all of the catalysts tried [13].
The observation of up to 68% ee in intramolecular cyclopropanations with
phenyliodonium ylides indicates that the mechanism proposed by Moriarty et al. cannot
be the main pathway of the reaction. Unfortunately, the lack of reactivity of diazo
compound 14a does not allow comparison with the enantioselectivities achieved with
the ylides, and it is not clear whether the less than 100% enantioselectivity must be
attributed to an inadequate choice of catalysts or to competing, unselective cyclo-
propanation pathways. Although we have not observed spontaneous cyclopropanations
of ylides in the absence of catalysts in the present investigation, such reactions have
been reported in the past not only by Moriarty et al. [7], but also by ourselves [6], and
for these reactions the mechanism outlined in Scheme 1, or a radical version thereof, is
plausible. The present results lend some support for a metal carbenoid intermediate in
the main pathway of the Cu-catalyzed ylide decomposition. However, this mechanistic

Helvetica Chimica Acta ± Vol. 84 (2001)
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hypothesis needs to be backed up with more experimental evidence. From the synthetic
point of view, the fact that enantioselective cyclopropanations with phenyliodonium
ylides are possible should open up new possibilities and a larger choice of catalysts for
metal carbenoid reactions.
Preparation of Ligands. Appropriate references for the synthesis of the known
ligands used in this work are given in the experimental part. (S)-N,N,N',N'-
Tetramethyl-[1,1'-binaphthalene]-2,2'-diamine (III) was prepared by methylation of
the commercially available diamine 17 (Scheme 4). Alkylation of (‡)-camphor (18)
with heptafluorobutanoyl chloride afforded 19, which reacted with [Cu(NO3)2] to give
complex IV. The bis[dihydrooxazole] IX, in turn, was prepared from (‡)-camphoric
acid (20a), which was converted to the dichloride 20b with PCl5 [22]. Condensation of
20b with l-tert-leucinol (ˆ(2S)-2-amino-3,3-dimethylbutan-1-ol) in the presence of
Et3N afforded diamide 21, which was converted to IX with TsCl in the presence of Et3N
and N,N-dimethylpyridin-4-amine (DMAP) [23].
Scheme 4
The dihydrooxazol-substituted binaphthalene Xb was synthesized according to the
method used for the tert-butyl analog Xa [24]: 1-bromo naphthalene-2-carboxylic acid
(22a) was converted to the acid chloride 22b with oxalyl chloride in the presence of a
catalytic quantity of DMF (Scheme 5). Reaction of 22b with (2S)-2-amino-3-cyclo-

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Helvetica Chimica Acta ± Vol. 84 (2001)
hexylpropan-1-ol hydrochloride (23) in the presence of Et3N afforded the amide, which
was converted without isolation to the dihydrooxazol 24 by means of the Burgess
reagent [25]. Ullmann coupling [26] of 24 with Cu in pyridine led to the binaphthalene
derivative Xb as a mixture of stereoisomers of 70% de. This contrasts with the synthesis
of the tert-butyl analogue Xa, which is fully diastereoselective. The de of Xb could be
slightly improved by HPLC separation; however, since this operation had practically no
effect on the enantioselectivity of the cyclopropanations, which was only marginal, the
separation of the diastereoisomers was not completed, and the absolute configuration
of the binaphthalene moiety was not determined. Bromo acid 22a was also the starting
material for XI: reaction with Meerweinꢀs salt afforded the imidate 25, which was
converted to the dihydrooxazole derivative 27 with (1R,2S)-1-aminoindan-2-ol (26).
Ullmann coupling resulted in the formation of XI with only 66% de. Attempted
separation of the diastereoisomers of XI was not successful.
Scheme 5
The pybox ligand XIIc was synthesized from pyridine-2,6-dicarbonyl dichloride
(28) and amino alcohol 23 via diamide 29 [27] (Scheme 6). Extension of known
methods [28] towards the preparation of 4',4'',5',5''-tetrasubstituted pybox ligands XV
failed. However, pyridine-2,6-dicarbonitrile (30) could be converted to the diimidate

Helvetica Chimica Acta ± Vol. 84 (2001)
1103
31 with NaOMe in MeOH, as described for pyridine-2-carbonitrile [29]. Condensation
of 31 with amino alcohol 32 in (CH2Cl)2 afforded the bis[dihydrooxazole] XVa in 78%
yield, and silylation of XVa with several trialkylsilyl chlorides gave the derivatized
ligands XVb ± d.
Scheme 6
This work was supported by the Swiss National Science Foundation (grants Nos. 20-52581.97 and 2027-
048156) and by the European Commission for Science, Research, and Development (COST Action D12). The
authors thank Mrs. A. Pinto and J.-P. Saulnier for the NMR spectra, and Ms. D. Klink for the mass spectra.
Experimental Part
General. See [30]. FC ˆ flash chromatography. GC: tR in min.
1. Allyl Diazomalonates 6 and Ylides 7 and Their Intramolecular Cyclopropanation. Allyl tert-Butyl 2-
Diazomalonate (6b). See [10].
Allyl Benzyl 2-Diazomalonate (6c). To monobenzyl malonate [31] (6.07 g, 31 mmol), allyl alcohol (3.63 g,
63 mmol), and N,N-dimethylpyridin-4-amine (DMAP; 382 mg, 3.12 mmol) in CH2Cl2 (30 ml), dicyclohex-
ylcarbodiimide (DCC; 12.9 g, 63 mmol) was added at 08. A white suspension precipitated while the mixture was
stirred at r.t. overnight. After filtration, the filtrate was extracted with 0.5n HCl (2 Â 30 ml). The org. layer was
dried (MgSO4) and evaporated, and the residue purified by bulb-to-bulb distillation: 5c (6.36 g, 87%). Colorless
oil. IR (NaCl): 2950w, 1734s, 1329s, 1271m, 1146s, 993m, 749m, 698m. 1H-NMR (500 MHz, CDCl3): 3.50

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Helvetica Chimica Acta ± Vol. 84 (2001)
(s, 2 H); 4.66 (dt, J ˆ 1.3, 6.0, 2 H); 5.22 (s, 2 H); 5.25 ± 5.29 (m, 1 H); 5.32 ± 5.38 (m, 1 H); 5.91 (ddt, J ˆ 6.0, 10.7,
11.6, 1 H); 7.35 ± 7.43 (m, 5 H, CH). 13C-NMR (125 MHz, CDCl3): 41.5 (t); 66.1 (t); 67.2 (t); 118.8 (t); 128.3 (d);
‡
128.4 (d); 128.6 (d); 131.4 (d); 135.2 (s); 166.0 (s); 166.2 (s). MS: 234 (5, M ), 108 (19), 107 (100), 100 (8), 92
‡
(7), 91 (70), 90 (7), 87 (14), 79 (12), 77 (7), 65 (8). HR-MS: 234.08920 (C13H14O4 ; calc. 234.08920).
To 5c (1.33 g, 5.68 mmol) in MeCN (5.0 ml), TsN3 [32] (1.12 g, 5.68 mmol) and K2CO3 (784 mg, 5.68 mmol)
in MeCN (10.0 ml) were added at r.t. The mixture was stirred overnight. After evaporation, the yellow residue
was dissolved in Et2O (50 ml), the org. layer washed with 10% aq. K2CO3 soln. (2 Â 50 ml), dried (MgSO4), and
evaporated to afford a yellow product, which was taken up in Et2O/hexane 1:5. After filtration and evaporation
of the filtrate, the residue was purified by FC (pentane/AcOEt 9 :1): 6c (1.23 g, 83%). Yellow oil. IR (NaCl):
3035m, 2141s, 1758s, 1732s, 1638s, 1643m, 1450m, 1392m, 1321s, 1303s, 1089m, 910s, 748s. 1H-NMR (500 MHz,
CDCl3): 4.76 (dt, J ˆ 1.3 and 5.7, 2 H); 5.28 ± 5.32 (m, 1 H); 5.31 (s, 2 H); 5.35 ± 5.41 (m, 1 H); 5.95 (ddt, J ˆ 5.6,
10.4, 11.3, 1 H); 7.34 ± 7.43 (m, 5 H). 13C-NMR (100 MHz, CDCl3): 66.0 (t); 67.0 (t); 118.9 (t); 128.2 (d); 128.4
‡
‡
(d); 128.6 (d); 131.4 (d); 135.3 (s); 160.6 (s); 160.8 (s). ESI-MS: 283.0 ([M ‡ Na] , C13H12N2NaO4 ; calc. 283.1).
1-(Allyloxy)-2-(tert-butoxy)-1,3-dioxo-2-(phenyliodonio)propan-2-ide (7b). To powdered KOH (261 mg,
4.00 mmol) in MeCN (3.0 ml), 5b [9] (200 mg, 1.0 mmol) in MeCN (2.0 ml) and diacetoxyiodobenzene (322 mg,
1.00 mmol) were added at 108 in small portions. After stirring at 108 for 45 min, the solvent was evaporated
and the residue dissolved in CH2Cl2 (5.0 ml). The soln. was poured on ice-water (5.0 ml) and the aq. phase
extracted with CH2Cl2 (3 Â 5 ml). The combined org. layer was dried (MgSO4) and evaporated: 7b as semi-solid
oil in yields varying between 55 and 80%. 1H-NMR (200 MHz, CDCl3): 1.45 (s, 9 H); 4.61 ± 4.68 (m, 2 H); 5.05 ±
5.43 (m, 2 H); 5.78 ± 6.04 (m, 1 H); 7.35 ± 7.62 (m, 3 H); 7.66 ± 7.73 (m, 2 H).
Intramolecular Cyclopropanation with Diazomalonates 6b,c: Typical Procedure. A soln. of [Cu(OTf)2]
(3.2 mg, 8.9 mmol, 0.02 equiv.) and bis[dihydrooxazole] Xa (4.9 mg, 9.7 mmol, 0.022 equiv.) was stirred in
(CH2Cl)2 (5.0 ml) at r.t. for 1 h. The temp. was raised to 658, and 6b (100 mg, 0.44 mmol) in (CH2Cl)2 (5.0 ml)
was added at once. The mixture was stirred at 658 for 16 h. After evaporation, the residue was purified by FC
(SiO2, pentane/AcOEt 80 :20): 8b (18 mg, 21%) of 74% ee.
Intramolecular Cyclopropanation with Ylide 7b: Typical Procedure. A soln. of [Cu(OTf)2] (6.4 mg, 18 mmol,
0.02 equiv.) and bis[dihydrooxazole] VIIc (7.3 mg, 19 mmol, 0.022 equiv.) was stirred in CH2Cl2 (10.0 ml) at r.t.
for 1 h. The mixture was cooled to 08, 7b (362 mg, 0.90 mmol) in CH2Cl2 (10.0 ml) added in one portion, and the
mixture then stirred at 08 for 4 h. After evaporation, the residue was purified by FC (SiO2, pentane/AcOEt
80 :20): 8b (82 mg, 46%) of 42% ee. Colorless solid.
tert-Butyl 2-Oxo-3-oxabicyclo[3.1.0]hexane-1-carboxylate (8b): GC (Lipodex E, 1108): tR 29.8 (1R,5R),
32.8 (1S,5S). M.p. 748 ([9]: m.p. 73 ± 748). [a]D20 ˆ 89.0 (c ˆ 0.50, CHCl3) for 74% ee ([33]: [a]D ˆ 105.5 (c ˆ 1.3,
CH2Cl2)). 1H-NMR (400 MHz, CDCl3): 1.28 ± 1.33 (m, 1 H); 1.50 (s, 9 H); 2.00 (dd, J ˆ 4.9, 7.9, 1 H); 2.63 ± 2.68
(m, 1 H); 4.16 (d, J ˆ 9.4, 1 H); 4.35 (dd, J ˆ 4.9, 0.4, 1 H). 13C-NMR (100 MHz): 20.3 (t); 27.5 (d); 27.9 (q); 29.9
(s); 66.8 (t); 82.8 (s); 165.5 (s); 170.6 (s).
Benzyl 2-Oxo-3-oxabicyclo[3.1.0]hexane-1-carboxylate (8c): GC (Lipodex E, 1308): tR 34.6, 51.0. [a]D20
ˆ
36.2 (c ˆ 0.81, CHCl3) for 42% ee. 1H-NMR (500 MHz, CDCl3): 1.33 (dd, J ˆ 5.1, 5.3, 1 H); 2.03 (dd, J ˆ 4.7,
8.2, 1 H); 2.64 ± 2.71 (m, 1 H); 4.11 (d, J ˆ 9.4, 1 H); 4.28 (dd, J ˆ 4.7, 9.4, 1 H); 5.15 (d, J ˆ 12.3, 1 H); 5.19
(d, J ˆ 12.6, 1 H, CH2); 7.23 ± 7.35 (m, 5 H, CH). 13C-NMR (125 MHz, CDCl3): 20.8 (t); 28.0 (d); 29.4 (s); 67.0
‡
(t); 67.4 (t); 128.1 (d); 128.4 (d); 128.6 (d); 135.1 (s); 166.5 (s); 170.2 (s). MS: 232 (9, M ), 126 (71), 125 (10), 108
(59), 107 (75), 98 (39), 91 (100), 90 (13), 83 (15), 82 (13), 80 (33), 79 (17), 77 (12), 69 (14), 65 (22), 53 (20), 51
‡
(14). HR-MS: 232.07403 (C13H12O4 ; calc. 232.07356).
2. Diazo Keto Ester 14a and Ylides 15a,b,d and Their Intramolecular Cyclopropanation. (2E,4E)-Deca-2,4-
dien-1-ol (10) [18]. (2E,4E)-Deca-2,4-dienal (9; tech., 90%) was purified by FC (pentane/AcOEt 98 :2). Then 9
(3.25g, 21.3 mmol) was reduced in Et2O (60 ml) with 1m DIBAL in THF (38 ml, 21.3 mmol) at 08. After 1 h, the
reaction was quenched with H2O (5 ml) and the mixture stirred until a gel was formed. After addition of solid
MgSO4, the gel precipitated and was removed by filtration. Evaporation of the filtrate afforded 10 (3.24 g, 98%)
as a colorless oil, which was used without further purification. IR (NaCl): 3330s (br.), 2955s, 2924s, 2855s, 1461w,
1087m, 987s. 1H-NMR (500 MHz, CDCl3): 0.92 (t, J ˆ 7.0, 3 H); 1.26 ± 1.38 (m, 4 H); 1.39 ± 1.47 (m, 2 H); 1.64 ±
1.70 (br. s, 1 H); 2.07 ± 2.14 (m, 2 H); 4.18 (d, J ˆ 6.0, 2 H); 5.70 ± 5.79 (m, 2 H); 6.07 (dd, J ˆ 10.7, 15.1, 1 H);
6.24 (dd, J ˆ 10.7, 15.5, 1 H). 13C-NMR (125 MHz): 14.0 (q); 22.5 (t); 28.9 (t); 31.4 (t); 32.6 (t); 63.5 (t); 129.3 (d);
‡
132.1 (d); 135.8 (d). MS: 154 (18, M ), 110 (15), 98 (14), 97 (18), 95 (10), 84 (74), 83 (84), 82 (15), 81 (33), 80
(16), 79 (35), 77 (15), 71 (10), 70 (53), 69 (42), 68 (26), 67 (61), 66 (10), 57 (31), 56 (35), 55 (100), 54 (34), 53
‡
(17), 51 (6). HR-MS: 154.1356 (C10H18O ; calc. 154.1358).
(2E,4E)-1-Bromodeca-2,4-diene (11) [18]. To Ph3P (5.30 g, 20.2 mmol) in MeCN (60 ml) at 08, Br2 (1.04 ml,
20.2 mmol) was added until the color of Br2 faded. A small amount of Ph3P was then added to remove unreacted

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Br2. The temp. was raised to r.t., and 10 (2.97 g, 19.2 mmol) in MeCN (25 ml) was added. After 10 min, the
mixture was poured into petroleum ether. The layers were separated, and the MeCN was repeatedly extracted
with petroleum ether (4 Â 100 ml). Evaporation gave a crude oil which was purified by bulb-to-bulb distillation
(0.2 mbar/1008): 3.55 g (85%) of 11. Colorless oil, which was used without further treatment. IR (NaCl): 2957s,
2926s, 2856m, 1652w, 1466w, 1200m, 986s. 1H-NMR (500 MHz, CDCl3): 0.82 (t, J ˆ 7.0, 3 H); 1.16 ± 1.28
(m, 4 H); 1.29 ± 1.37 (m, 2 H); 1.99 ± 2.05 (m, 2 H); 3.96 (d, J ˆ 8.2, 2 H); 5.65 ± 5.74 (m, 2 H); 5.96 (dd, J ˆ 11.0,
15.1, 1 H); 6.19 (dd, J ˆ 11.0, 14.8, 1 H). 13C-NMR (125 MHz): 14.0 (q); 22.5 (t); 28.7 (t); 31.4 (t); 32.6 (t); 33.9
‡
‡
(t); 126.1 (d); 128.7 (d); 135.4 (d); 137.9 (d). MS: 218 (5, M ), 216 (5, M ), 137 (36), 95 (23), 81 (33), 80 (21), 67
(100), 55 (12). HR-MS: 216.0487 (C10H17 79Br ; calc. 216.0514).
‡
Alkyl (6E,8E)-3-Oxotetradeca-6,8-dienoates 13a,b,d: General Procedure [19]. To NaH (656 mg, 16.4 mmol)
in THF (30 ml) at 08, 2-methyl-1-(1-methylethyl)propyl 3-oxobutanoate [34] (12d; 3.29 g, 16.4 mmol) was
added slowly. After stirring for 10 min at 08, 1.6m BuLi in hexane (16.4 ml, 16.4 mmol) was added slowly, and the
orange soln. was stirred for 10 additional min. Crude 11 (3.24 g, 14.9 mmol) in THF (5 ml) was added to the
dianion. The mixture was stirred for 30 min, whereupon it became colorless. It was decomposed with conc. HCl
soln. (5.0 ml in 13 ml of H2O) and Et2O (40 ml) and extracted with Et2O (2 Â 25 ml). The combined org. layer
was washed (H2O) until neutrality, dried (MgSO4), and evaporated, and the residue purified by FC (pentane/
AcOEt 95 :5): 13d (3.97 g, 79%). Colorless oil.
Methyl (6E,8E)-3-Oxotetradeca-6,8-dienoate (13a) [14][16]. Yield 76%. 1H-NMR (200 MHz, CDCl3):
0.83 ± 0.92 (m, 3 H); 1.18 ± 1.45 (m, 6 H); 2.03 (q, J ˆ 6.9, 2 H); 2.25 ± 2.42 (m, 2 H); 2.63 (t, J ˆ 7.3, 3 H); 3.44
(s, 2 H); 3.73 (s, 3 H); 5.45 ± 5.70 (m, 2 H); 5.85 ± 6.12 (m, 2 H).
tert-Butyl (6E,8E)-3-Oxotetradeca-6,8-dienoate (13b). From 11 and 12b. Yield 71%. IR (NaCl): 2958m,
2927s, 1736s, 1719s, 1368m, 1250m, 1150s, 988s. 1H-NMR (500 MHz, CDCl3): 0.89 (t, J ˆ 6.9, 3 H); 1.22 ± 1.33
(m, 4 H); 1.35 ± 1.41 (m, 2 H); 1.47 (s, 9 H); 2.02 ± 2.08 (m, 2 H); 2.32 ± 2.39 (m, 2 H); 2.63 (t, J ˆ 7.2, 2 H); 3.35
(s, 2 H); 5.48 ± 5.64 (m, 2 H); 5.93 ± 6.07 (m, 2 H). 13C-NMR (125 MHz, CDCl3): 14.0 (q); 22.6 (t); 26.4 (t); 28.0
(q); 29.0 (t); 31.4 (t); 32.6 (t); 42.5 (t); 50.7 (t); 82.0 (s); 129.4 (d); 129.8 (d); 131.5 (d); 133.6 (d); 166.4 (s); 202.6
‡
(s). MS: 294 (1, M ), 238 (21), 150 (10), 149 (10), 137 (13), 136 (48), 121 (16), 109 (12), 107 (10), 95 (14), 93
‡
(12), 81 (20), 79 (39), 69 (12), 67 (31), 59 (15), 57 (100), 55 (17). HR-MS: 294.2223 (C18H30O3 ; calc. 294.2195).
2-Methyl-1-(1-methylethyl)propyl (6E,8E)-3-Oxotetradeca-6,8-dienoate (13d). From 11 and 12d. Yield
1
79%. IR (NaCl): 2982s, 2928s, 2874m, 1738s, 1714s, 1643m, 1465w, 1237m, 987s. H-NMR (500 MHz, CDCl3):
0.90 (d, J ˆ 6.6, 6 H); 0.92 (t, J ˆ 7.0, 3 H); 0.93 (d, J ˆ 6.6, 6 H); 1.26 ± 1.36 (m, 4 H); 1.37 ± 1.44 (m, 2 H); 1.89 ±
1.99 (m, 2 H); 2.04 ± 2.11 (m, 2 H); 2.36 ± 2.43 (m, 2 H); 2.69 (t, J ˆ 7.2, 2 H); 3.50 (s, 2 H); 4.67 (t, J ˆ 6.0, 1 H);
5.52 ± 5.67 (m, 2 H); 5.96 ± 6.11 (m, 2 H). 13C-NMR (125 MHz): 14.0 (q); 17.2 (q); 19.5 (q); 22.5 (t); 26.4 (t); 29.0
(t); 29.4 (d); 31.4 (t); 32.5 (t); 42.9 (t); 49.4 (t); 84.1 (d); 129.3 (d); 129.8 (d); 131.6 (d); 133.7 (d); 167.1 (s); 202.1
‡
(s). MS: 336 (1, M ), 238 (12), 221 (11), 137 (11), 136 (28), 109 (10), 81 (10), 79 (14), 67 (20), 57 (100), 55 (11).
‡
HR-MS: 336.2622 (C21H36O3 ; calc. 336.2664).
Methyl (6E,8E)-2-Diazo-3-oxotetradeca-6,8-dienoate (14a). See [14][15].
Phenyliodonium Ylides 15a,b,d: Typical Procedure. To KOH (116 mg, 1.78 mmol) in MeOH (2.0 ml) at 08,
13d (150 mg, 0.44 mmol) in MeOH (2.0 ml) was added slowly. (Diacetoxy)iodobenzene (144 mg, 0.44 mmol)
was added in portions, and the mixture was stirred for 10 min. The yellow soln. was then poured on ice-water
(5 ml), which was extracted with CH2Cl2 (3 Â 5 ml). The org. layer was dried (MgSO4) and evaporated: 15d
(211 mg, 89%). Yellow oil.
1
1-Methoxy-1,3-dioxo-2-(phenyliodonio)tetradeca-6,8-dien-2-ide (15a) [16]. Yield 86%. H-NMR (CDCl3):
0.82 ± 0.91 (m, 3 H); 1.19 ± 1.43 (m, 6 H); 2.03 (q, J ˆ 7.0, 2 H); 2.24 ± 2.40 (m, 2 H); 2.60 (t, J ˆ 7.1, 2 H); 3.71
(s, 3 H); 5.45 ± 5.70 (m, 2 H); 5.85 ± 6.12 (m, 2 H); 7.30 ± 7.55 (m, 3 H); 7.68 ± 7.75 (m, 2 H).
1-(tert-Butoxy)-1,3-dioxo-2-(phenyliodonio)tetradeca-6,8-dien-2-ide (15b). Yield 87%. Oil. 1H-NMR
(200 MHz, CDCl3): 0.87 (t, J ˆ 7.0, 3 H); 1.20 ± 1.40 (m, 6 H); 1.43 (s, 9 H); 1.95 ± 2.10 (m, 2 H); 2.35 ± 2.48
(m, 2 H); 3.00 ± 3.10 (m, 1 H); 3.40 ± 3.50 (m, 1 H); 5.40 ± 5.75 (m, 1 H); 5.85 ± 6.10 (m, 1 H); 7.30 ± 7.56
(m, 3 H); 7.68 ± 7.76 (m, 2 H).
1-[2-Methyl-1-(1-methylethyl)propoxy]-1,3-dioxo-2-(phenyliodonio)tetradeca-6,8-dien-2-ide (15d). Yield
89%. 1H-NMR (200 MHz, CDCl3): 0.79 (d, J ˆ 6.7, 6 H); 0.84 (d, J ˆ 6.8, 6 H); 0.87 (t, J ˆ 6.4, 3 H); 1.11 ±
1.46 (m, 6 H); 1.72 ± 2.09 (m, 4 H); 2.31 ± 2.49 (m, 2 H); 3.15 (t, J ˆ 2 H); 4.58 (t, J ˆ 6.2, 1 H); 5.43 ± 5.73
(m, 2 H); 5.88 ± 6.11 (m, 2 H); 7.28 ± 7.42 (m, 2 H); 7.44 ± 7.54 (m, 1 H); 7.65 ± 7.78 (m, 2 H).
Intramolecular Cyclopropanation by Diazo Decomposition of 14a. The diazo decomposition of 14a was
carried out according to the procedure used for 6 with IV (5 mol-%) as catalyst in (CH2Cl)2 at 658 to afford
racemic 16a (45%). For data of 16a, see below.

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Intramolecular Cyclopropanation of Phenyliodonium Ylides 15a,b,d: Typical Procedure. The appropriate
ligand (11.2 mmol) and [Cu(OTf)2] (3.4 mg, 10 mmol) were stirred in CH2Cl2 (6.0 ml) for 1 h. Ylide 15d (252 mg,
0.47 mmol) in CH2Cl2 (6.0 ml) was added at 08, and the mixture was stirred overnight at 08. After evaporation,
the residue was purified by FC (pentane/AcOEt 95 :5) to give 16d. For yields and enantioselectivity, see Table 4.
Methyl ꢁexoꢀ-6-[(1E)-Hept-1-enyl)-2-oxobicyclo[3.1.0]hexane-1-carboxylate (16a) [14][16]. For yields and
enantioselectivities, see Table 4. GC (Lipodex E, 1308): tR 79.5, 89.7. [a]D ˆ ‡34.4 (c ˆ 0.53, CHCl3) for 42% ee.
1H-NMR (200 MHz, CDCl3): 0.83 ± 0.92 (m, 3 H); 1.08 ± 1.53 (m, 6 H); 1.80 ± 2.56 (m, 8 H); 3.64 (s, 3 H); 5.12
(dd, J ˆ 8.1, 15.1, 1 H); 5.63 (dt, J ˆ 7.5, 15.2, 1 H).
tert-Butyl ꢁexoꢀ-6-[(1E)-Hept-1-enyl]-2-oxobicyclo[3.1.0]hexane-1-carboxylate (16b). Colorless oil. HPLC
(OJ, hexane/iPrOH 99 :1, 0.5 ml/min). tR 13.3, 14.7. [a]2D0
ˆ
47.9 (c ˆ 0.64, CHCl3) for 68% ee. IR (NaCl):
2957m, 2927s, 2872m, 1732s, 1715s, 1366m, 1249m, 1156s. 1H-NMR (500 MHz, CDCl3): 0.87 (t, J ˆ 7.0, 3 H);
1.20 ± 1.38 (m, 6 H); 1.47 (s, 9 H); 1.95 ± 2.06 (m, 3 H); 2.11 ± 2.24 (m, 3 H); 2.26 (dd, J ˆ 5.4, 8.9, 1 H); 2.55 ±
2.60 (m, 1 H); 5.23 (ddt, J ˆ 1.3, 9.1, 15.4, 1 H); 5.73 (dt, J ˆ 6.9, 15.4, 1 H). 13C-NMR (125 MHz, CDCl3): 14.0
(q); 20.7 (t); 22.4 (t); 28.1 (q); 28.8 (t); 31.3 (t); 32.5 (t); 33.5 (t); 33.8 (d), 37.4 (d); 46.1 (s); 81.6 (s); 123.4 (d);
‡
135.7 (d); 165.0 (s); 206.3 (s). MS: 292 (0.5, M ), 194 (18), 162 (10), 161 (18), 149 (14), 148 (53), 140 (33), 135
(11), 127 (11), 124 (15), 123 (18), 122 (10), 110 (13), 109 (17), 96 (12), 93 (13), 91 (18), 82 (11), 79 (26), 77 (15),
67 (11), 59 (10), 57 (100), 56 (16), 55 (36), 53 (11).
2-Methyl-1-(1-methylethyl)propyl ꢁexoꢀ-6-[(1E)-Hept-1-enyl]-2-oxobicyclo[3.1.0]hexane-1-carboxylate
(16d). HPLC (AD, hexane/iPrOH 99 :1, 0.5 ml/min): tR 11.8, 14.0. [a]D20 ˆ ‡36.4 (c ˆ 0.98, CHCl3) for 52% ee.
IR (NaCl): 2961s, 2931s, 2874s, 1732s, 1714s, 1464m, 1372m, 1198m, 985w. 1H-NMR (500 MHz, CDCl3): 0.88
(d, J ˆ 6.9, 3 H); 0.90 (d, J ˆ 6.9, 3 H); 0.91 (t, J ˆ 7.0, 3 H); 0.94 (d, J ˆ 7.0, 3 H); 1.01 (d, J ˆ 6.6, 3 H); 1.22 ± 1.40
(m, 6 H); 1.90 ± 2.03 (m, 4 H); 2.04 ± 2.10 (m, 1 H); 2.17 ± 2.31 (m, 3 H); 2.37 (dd, J ˆ 9.1, 5.3, 1 H); 2.66
(m, 1 H); 4.71 (dd, J ˆ 6.6, 5.3, 1 H); 5.25 (dd, J ˆ 15.4, 9.1, 1 H); 5.77 (dt, J ˆ 13.6, 6.6, 1 H). 13C-NMR
(125 MHz): 14.0 (q); 16.8 (q); 17.9 (q); 19.4 (q); 19.7 (q); 20.8 (t); 22.5 (t); 28.7 (t); 29.3 (d); 29.4 (d); 31.4 (t);
‡
32.6 (t); 33.6 (t); 33.9 (d); 37.8 (d); 45.8 (s); 84.2 (s); 123.9 (d); 135.7 (d); 166.3 (s); 205.7 (s). MS: 334 (1, M ),
237 (15), 236 (17), 219 (47), 218 (17), 194 (37), 162 (13), 161 (16), 149 (15), 148 (63), 140 (60), 137 (10), 135
(10), 127 (13), 124 (14), 123 (16), 110 (10), 109 (14), 98 (13), 97 (17), 91 (16), 83 (16), 79 (18), 77 (12), 57 (100),
‡
55 (37). HR-MS: 334.2514 (C21H34O3 ; calc. 334.2508).
3. Ligands and Catalysts. The known ligands and catalysts used in this work were either purchased (I and II)
or were synthesized according to published procedures in the case of V [35], VI and VIIa,b [23][36], VIIIa [37],
VIIIb [38], Xa [26], XIIa,b and XIII [27], XIII [39], and XVI [40].
(S)-N,N,N',N'-Tetramethyl-[1,1'-binaphthalene]-2,2'-diamine (III). To 20% H2SO4 soln. (1.00 ml) and 40%
aq. formaldehyde (554 ml, 7.40 mmol) in THF (1.0 ml), (S)-[1,1'-binaphthalene]-2,2'-diamine (17; 150 mg,
0.53 mmol) in THF (10 ml) and NaBH4 (291 mg, 7.40 mmol) were added simultaneously. The mixture was
stirred for 15 min at r.t. and was then poured on 2% aq. KOH soln. (50 ml). The soln. was extracted with AcOEt
(3 Â 20 ml), the combined org. layer dried (MgSO4) and evaporated, and the crude product purified by
recrystallization (benzene/EtOH 1 :1): colorless crystals (152 mg, 85%). M.p. 255 ([41]: m.p. 252 ± 2568). [a]D20
ˆ
‡184 (c ˆ 1.05, C6H6) ([41]: [a]2D0 (ent-III) ˆ 50 (c ˆ 0.05, dioxane)). IR (CHCl3): 3014m, 1618w, 1595w, 1356w,
1
1224m, 746s. H-NMR (500 MHz, CDCl3): 2.49 (s, 12 H); 7.15 ± 7.21 (m, 4 H); 7.26 ± 7.32 (m, 2 H); 7.49 (d, J ˆ
9.1, 2 H); 7.82 (d, J ˆ 7.9, 2 H); 7.89 (d, J ˆ 8.8, 2 H). 13C-NMR (125 MHz): 43.4 (q); 120.6 (d); 123.3 (d); 125.9
‡
(d); 126.1 (d); 126.3 (s); 127.7 (d); 128.4 (d); 129.7 (s); 134.7 (s); 149.7 (s). MS: 340 (13, M ), 294 (15), 185 (14),
‡
184 (100), 183 (6), 170 (6), 78 (7). HR-MS: 340.1940 (C24H24N2 ; calc. 340.1939).
Bis{3-[2,2,3,3,4,4,4-Heptafluoro-(1-oxo-kO)butyl]-1,7,7-trimethylbicyclo[2.2.1]heptan-2-onato-kO}copper
(IV). 3-(2,2,3,3,4,4,4-Heptafluoro-1-hydroxybutylidene)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one (19). A soln.
of 1.5m tBuLi (53.3 ml, 80.0 mmol) in pentane was added to (‡)-camphor (18; 12.2 g, 80.0 mmol) in THF (60 ml)
at 788. After 15 min, heptafluorobutanoyl chloride [42] (9.30 g, 40.0 mmol) was added slowly. The temp. was
raised to 258, and the mixture was stirred overnight. After addition of aq. AcOH soln. (80 ml) and pentane
(40 ml), the org. phase was evaporated, and the residue was dissolved in MeOH (60 ml). A suspension of
[Cu(OAc)2] (14.5 g, 80 mmol) in H2O (140 ml) was added, and the resulting Cu-chelate was extracted with
hexane (3 Â 200 ml). A deep-green solid was obtained after evaporation of the solvent. Residual camphor was
removed by sublimation at 1408/2 Torr. The free ligand 19 was liberated by dissolution of the product in Et2O
(400 ml) and washing with 10% H2SO4 soln. (2 Â 100 ml). The combined org. layer was washed with sat.
NaHCO3 soln. (100 ml) and evaporated, and the residue distilled at 718/1 Torr: pure 19 (10.2 g, 74%). [a]D20
ˆ
‡132.9 (c ˆ 1.41, CHCl3) ([43]: [a]2D0 ˆ ‡123 (c ˆ 2.6, CHCl3)). IR (NaCl): 2965m, 1700s, 1643m, 1340m, 1219s,
1120s, 1043m, 955m, 744m. 1H-NMR (400 MHz, CDCl3): 0.83 (s, 3 H); 0.97 (s, 3 H); 1.02 (s, 3 H); 1.41 ± 1.53
(m, 2 H); 1.73 ± 1.83 (m, 1 H); 2.04 ± 2.15 (m, 1 H); 2.84 ± 2.88 (m, 1 H); 11.65 ± 11.90 (br. s, 1 H). 13C-NMR

Helvetica Chimica Acta ± Vol. 84 (2001)
1107
(100 MHz): 8.5 (q); 18.2 (q); 20.3 (q); 26.7 (t); 30.1 (t); 47.5 (d); 49.0 (s); 58.0 (s); 120.6 (s); 148.4 (s); 214.0 (s).
‡
19F-NMR (376 MHz, CDCl3): 36.1 ± 36.3 (m, 2 F); 43.8 ± 46.1 (m, 2 F); 82.9 ± 83.1 (m, 3 F). MS: 348 (100, M ),
333 (34), 320 (46), 305 (33), 179 (10), 151 (40), 123 (22), 119 (15), 109 (10), 108 (16), 95 (21), 83 (10), 55 (16).
‡
HR-MS: 348.0974 (C14H15F7O2 ; calc. 348.0960).
Copper Complex IV. To a soln. of [Cu(NO3)2 ´ 3 H2O] (2.78 g, 11.5 mmol) in H2O (28 ml) and aq. NH3 soln.
(4.20 ml), ligand 19 (2.00 g, 5.76 mmol) was slowly added. The aq. layer was extracted with Et2O (3 Â 40 ml), the
org. layer dried (MgSO4) and evaporated, and the residue recrystallized from EtOH: pure IV (2.13 g, 97%).
Green crystals. M.p. 1348. [a]D20
ˆ
21.9 (c ˆ 0.04, CHCl3). IR (CHCl3): 2967m, 1681s, 1522s, 1344m, 1260m,
1232s, 1198m, 1178m, 1119m, 1082w, 1046w, 956w, 901w, 788m, 720s. ESI-MS: 779.9 (C2862CuF14H28O4Na ; calc.
‡
‡
780.1); 781.7 (C2864CuF14H28O4Na ; calc. 782.1).
2,2'-[(1R,3S)-2,2-Dimethylcyclopentane-1,3-diyl]bis[(4S)-4-(tert-butyl)-4,5-dihydrooxazole]
(IX).
(1R,3S)-1,2,2-Trimethylcyclopentane-1,3-dicarbonyl Dichloride (20b) [26]. To a suspension of PCl5 (10.4 g,
50 mmol) in hexane (20 ml) at 08, (‡)-camphoric acid (20a; 5.00 g, 25 mmol) was added in small portions. The
mixture was stirred for 1 h at 08 and for 1 h at r.t. After evaporation, the yellow residue was distilled at 708/
0.1 Torr: 20b (5.05 g, 85%). Yellow oil. [a]2D0 ˆ ‡34.7 (c ˆ 2.78, CHCl3). IR (neat): 2979m, 1786s, 1458w, 1382w,
1040w, 930m, 800m. 1H-NMR (200 MHz, CDCl3): 1.08 (s, 3 H); 1.38 (s, 3 H); 1.47 (s, 3 H); 1.62 ± 1.79 (m, 1 H);
1.95 ± 2.33 (m, 2 H); 2.52 ± 2.70 (m, 1 H); 3.23 ± 3.34 (m, 1 H). 13C-NMR (50 MHz): 20.6 (q); 21.9 (q); 22.8 (q);
‡
23.8 (t); 33.6 (t); 47.7 (s); 64.5 (d); 65.5 (s); 174.5 (s); 176.8 (s). MS: 201 (3, [M Cl] ), 175 (5), 173 (19), 172
(8), 165 (8), 164 (8), 138 (18), 137 (100), 136 (89), 131 (7), 129 (10), 118 (5), 110 (11), 109 (97), 108 (38), 96
(39), 95 (28), 93 (10), 91 (9), 89 (7), 83 (55), 82 (40), 81 (9), 79 (10), 77 (16), 69 (59), 68 (51), 67 (33), 65 (6), 55
‡
(60), 53 (23). HR-MS: 201.07000 (C10H14O2Cl ; calc. 201.0682).
(1R,3S)-N,N'-Bis[(1R)-1-(hydroxymethyl)-2,2-dimethylpropyl]-1,2,2-trimethylcyclopentan-1,3-diamide
(21). To l-tert-leucinol (ˆ(2S)-2-amino-3,3-dimethylbutan-1-ol; 178 mg, 1.52 mmol) in CH2Cl2 (2.0 ml) at 08,
Et3N (529 ml, 3.80 mmol, 5 equiv.) and 20b (180 mg, 0.76 mmol) were added slowly. The mixture was stirred at
258 for 1 h. After evaporation, the crude product was purified by FC (CH2Cl2/MeOH 95 :5): 21 (273 mg, 90%).
Colorless solid. M.p. 1758. [a]D20
ˆ
53.5 (c ˆ 2.09, CHCl3). IR (KBr): 3308s, 2960s, 1630s, 1534s, 1475m, 1367m,
1053m. 1H-NMR (400 MHz, CDCl3): 0.91 (s, 3 H); 0.95 (s, 9 H); 0.96 (s, 9 H); 1.08 (s, 3 H); 1.21 (s, 3 H); 1.66 ±
1.77 (m, 1 H); 1.86 ± 1.97 (m, 1 H); 2.08 ± 2.18 (m, 1 H); 2.23 ± 2.37 (m, 1 H); 2.96 ± 3.04 (m, 1 H); 3.34 ± 3.44
(m, 1 H); 3.45 ± 3.63 (m, 3 H); 3.75 ± 3.92 (m, 4 H); 5.84 (d, J ˆ 8.4, 1 H); 5.98 (d, J ˆ 8.9, 1 H). 13C-NMR
(100 MHz): 19.7 (q); 20.8 (q); 25.1 (q); 25.4 (t); 27.0 (q); 27.1 (q); 33.2 (s); 33.4 (s); 34.7 (t); 47.1 (s); 55.8 (d); 56.6
‡
(s); 59.6 (d); 59.7 (d); 63.2 (t); 63.5 (t); 174.6 (s); 178.8 (s). MS: 398 (3, M ), 367 (13), 283 (10), 282 (55), 264
(22), 255 (16), 254 (100), 236 (32), 213 (57), 195 (30), 186 (37), 168 (24), 144 (11), 137 (14), 118 (13), 111 (12),
‡
109 (34), 95 (16), 86 (48), 83 (27), 69 (34), 60 (11), 57 (23), 55 (25), 45 (11). HR-MS: 398.3187 (C22H42N2O4
calc. 398.1444).
;
Ligand IX. To TsCl (299 mg, 1.6 mmol, 2.5 equiv.) in CH2Cl2 (2.0 ml), 21 (250 mg, 0.63 mmol), N,N-
dimethylpyridin-4-amine (8 mg), and Et3N (386 ml, 4.4 equiv.) in CH2Cl2 (3.0 ml) were added. The mixture was
stirred for 2 d, then diluted with CH2Cl2 (5.0 ml), and washed with sat. NH4Cl soln. (10 ml). After the usual
workup, the crude product was purified by FC (hexane/AcOEt 80 :20): IX (195 mg, 85%). Colorless solid.
[a]2D0
ˆ
123 (c ˆ 1.39, CHCl3). IR (KBr): 2960s, 1643s, 1478s, 1381s, 1361s, 1292m, 1262s, 1211m, 1191s, 1169s,
1
1100s, 1043m, 989s, 920s. H-NMR (400 MHz, CDCl3): 0.88 (s, 12 H); 0.90 (s, 9 H); 1.03 (s, 3 H); 1.20 (s, 3 H);
1.62 ± 1.73 (m, 1 H); 1.99 ± 2.11 (m, 1 H); 2.12 ± 2.25 (m, 2 H); 2.96 ± 3.04 (m, 1 H); 3.76 ± 3.88 (m, 2 H); 3.94 ±
4.02 (m, 2 H); 4.09 ± 4.19 (m, 2 H). 13C-NMR (50 MHz): 20.4 (q); 25.0 (q); 25.6 (t); 26.0 (q); 26.1 (q); 33.5 (s);
‡
33.8 (s); 35.3 (t); 46.8 (s); 48.1 (d); 50.7 (s); 68.1 (t); 75.1 (d); 75.4 (d); 168.8 (s); 172.0 (s). MS: 362 (6, M ), 347
(14), 306 (22), 305 (100), 205 (20), 196 (10), 195 (50), 182 (10), 181 (28), 169 (13), 168 (90), 57 (11), 55 (10).
‡
HR-MS: 362.2927 (C22H38N2O2 ; calc. 362.2933).
2,2'-([1,1'-Binaphthalene]-2,2'-diyl)bis[(4S)-4-(cyclohexylmethyl)-4,5-dihydrooxazole] (Xb). (4S)-2-(1-
Bromonaphthalen-2-yl)-4-(cyclohexylmethyl)-4,5-dihydrooxazole (24). To 1-bromonaphthalene-2-carboxylic
acid (22a; 600 mg, 2.39 mmol) in CH2Cl2 (15 ml), oxalyl chloride (809 ml, 9.56 mmol) was added slowly, followed
by 3 drops of DMF. The mixture became transparent and was allowed to stand at r.t. overnight. The solvent was
evaporated and the residue dried in vacuo. The crude chloride 22b was dissolved in CH2Cl2 (30 ml) and added at
108 to a soln. of (2S)-2-amino-3-cyclohexylpropan-1-ol hydrochloride (23; 509 mg, 2.63 mmol) and Et3N
(677 ml, 6.69 mmol). The mixture was stirred at r.t. overnight. After evaporation, the residue was treated with
sat. NaCl soln. (15 ml) and extracted with CH2Cl2 (3 Â 30 ml). The combined org. layer was dried (MgSO4) and
evaporated. The resulting solid was dissolved in THF (15 ml), and Burgess reagent [25] ([(methoxycarbo-
nyl)sulfamoyl]triethylammonium hydroxide; 568 mg, 2.38 mmol) was added. After 24 h stirring, the solvent was
evaporated and the remaining yellow oil purified by FC (hexane/AcOEt 95 :5): 24 (756 mg, 85%). Slightly

1108
Helvetica Chimica Acta ± Vol. 84 (2001)
yellow solid. M.p. 708. [a]2D0 ˆ 54.4 (c ˆ 3.01, CH2Cl2). IR (CHCl3): 3014m, 2925s, 2360s, 1668m. 1H-NMR
(400 MHz, CDCl3): 0.95 ± 1.10 (m, 2 H); 1.14 ± 1.39 (m, 3 H); 1.44 ± 1.53 (m, 1 H); 1.54 ± 1.65 (m, 1 H); 1.66 ±
1.93 (m, 6 H); 4.11 (dd, J ˆ 7.8, 7.8, 1 H); 4.44 ± 4.54 (m, 1 H); 4.61 (dd, J ˆ 8.1, 9.4, 1 H); 7.55 ± 7.70 (m, 3 H);
7.81 ± 7.90 (m, 2 H); 8.43 (d, J ˆ 8.6, 1 H). 13C-NMR (100 MHz): 26.1 (t); 26.2 (t); 26.5 (t); 33.4 (t); 33.5 (t); 34.8
(d); 44.2 (t); 65.0 (d); 73.5 (t); 123.1 (s); 126.7 (d); 127.5 (d); 127.6 (d); 127.8 (d); 128.1 (d); 128.2 (d); 128.6 (s);
‡
‡
132.2 (s); 134.8 (s); 163.6 (s). MS: 373 (10, M ), 371 (10, M ), 292 (24), 291 (16), 289 (19), 276 (32), 274 (32),
252 (16), 250 (18), 236 (11), 235 (92), 234 (17), 233 (100), 210 (31), 196 (30), 167 (30), 153 (14), 152 (11), 126
(24), 55 (15). HR-MS: 371.0912 (C20H2279BrNO ; calc. 371.0885), 373.0858 (C20H2281BrNO ; calc. 373.0864).
2,2'-([1,1'-Binaphthalene]-2,2'diyl)bis[(4S)-4-(cyclohexylmethyl)-4,5-dihydrooxazole] (Xb). Bromide 24
(740 mg, 1.99 mmol) was dried by azeotropic distillation with benzene (3 Â 15 ml). Activated Cu powder
(3.16 g, 49.7 mmol) and freshly distilled pyridine (20 ml) were added, and the mixture was heated to reflux for
24 h. The solvent was evaporated, the residue dissolved in CH2Cl2, and the remaining Cu removed by filtration
through Celite. The org. phase was extracted with 20% NH4OH soln. (50 ml) and washed repeatedly with sat.
NH4Cl, until the blue color of the soln. faded. The org. layer was dried (MgSO4) and evaporated and the residue
purified by FC (SiO2, pentane/AcOEt 98 :2): Xb (367 mg, 63%). Colorless foam, containing two stereoisomers
‡
‡
in a 85 :15 ratio. [a]D20
ˆ
120.1 (c ˆ 1.02, CHCl3). IR (CHCl3): 2925s, 2359w, 2852m, 1646m, 1448m, 750s.
1H-NMR (500 MHz, CDCl3): 0.69 ± 0.81 (m, 2 H); 0.88 ± 1.15 (m, 14 H); 1.32 ± 1.39 (m, 2 H); 1.43 ± 1.57
(m, 8 H); 3.38 (dd, J ˆ 7.5, 7.6, 2 H); 3.70 (dd, J ˆ 8.2, 9.1, 2 H); 3.82 ± 3.90 (m, 2 H); 7.15 ± 7.22 (m, 4 H);
7.36 ± 7.41 (m, 2 H); 7.80 ± 7.89 (m, 4 H); 7.97 (d, J ˆ 8.5, 2 H). 13C-NMR (125 MHz, CDCl3): 26.1 (t); 26.5 (t);
33.1 (t); 33.3 (t); 34.3 (d); 43.7 (t); 64.1 (d); 72.8 (t); 126.0 (s); 126.1 (d); 126.3 (d); 126.7 (d); 127.0 (d); 127.5 (d);
‡
127.8 (d); 132.9 (s); 134.2 (s); 137.8 (s); 163.6 (s). MS: 584 (38, M ), 487 (23), 445 (10), 419 (35), 418 (100), 347
(19), 307 (11), 306 (43), 281 (14), 81 (15), 55 (21). HR-MS: 584.3387 (C40H44N2O2 ; calc. 584.3403).
‡
2,2'-([1,1'-Binaphthalene]-2,2'-diyl)bis[(3aR,8aS)-8,8a-dihydro-3aH-indeno[1,2-d]oxazole] (XI). 1-Bromo-
naphthalene-2-carboxamide (22c). 1-Bromonaphthalenecarboxylic acid (22a; 1.00 g, 3.98 mol) and SOCl2
(2.90 ml, 40 mmol) were refluxed for 3 h, after which the excess of SOCl2 was distilled off. The residue
(1.05 g) was dried in vacuo, then dissolved in Et2O, and gaseous NH3 was passed through the soln. for 30 min.
The precipitate was filtered, washed with H2O, and recrystallized in EtOH to afford 22c. Colorless crystals
(946 mg, 95%). M.p. 2048. IR (CHCl3): 3019s, 1677s, 1218m, 770s, 720s. 1H-NMR (400 MHz, CD3OD): 7.46
(d, J ˆ 8.3, 1 H); 7.57 ± 7.62 (m, 1 H); 7.63 ± 7.68 (m, 1 H); 7.88 ± 7.94 (m, 2 H); 8.33 (d, J ˆ 8.8, 1 H). 13C-NMR
(100 MHz): 118.6 (s); 124.2 (d); 127.0 (d); 127.2 (d); 127.8 (d); 127.9 (d); 128.0 (d); 131.7 (s); 134.4 (s); 136.7 (s);
‡
‡
172.5 (s). MS: 251 (65, M ), 250 (37), 249 (69, M ), 248 (29), 234 (13), 233 (97), 232 (14), 231 (100), 205 (29),
203 (28), 126 (13), 125 (16), 124 (76), 74 (12), 73 (14), 72 (13), 61 (41), 48 (10). HR-MS: 248.9797
(C11H879BrNO ; calc. 248.9789), 250.9776 (C11H881BrNO ; calc. 250.9769).
‡
‡
(3aR,8aS)-2-(1-Bromonaphthalen-2-yl)-8,8a-dihydro-3aH-indeno[1,2-d]oxazole (27). To amide 22c
(617 mg, 2.47 mol) in (CH2Cl)2 (20 ml) was added, in portions, dry (Me3O)BF4 (469 mg, 2.47 mmol). The
soln. was stirred overnight at r.t., whereupon (1R,2S)-1-amino-2,3-dihydro-1H-inden-2-ol (26; 405 mg,
2.71 mmol) was added, and the mixture was refluxed overnight. After cooling, it was poured on 5% aq.
NaHCO3 soln. (10 ml) and extracted with CH2Cl2 (3 Â 20 ml). The combined org. layer was dried (MgSO4) and
evaporated. FC (SiO2, pentane/AcOEt 90 :10) of the residue afforded 27 (459 mg, 51%). Colorless solid.
[a]2D0 ˆ ‡167.0 (c ˆ 0.50, CHCl3). 1H-NMR (500 MHz, CDCl3): 3.51 (dd, J ˆ 17.9, 1.9, 1 H); 3.57 (dd, J ˆ 17.9,
6.3, 1 H); 5.61 ± 5.66 (m, 1 H); 5.86 (d, J ˆ 8.2, 1 H); 7.29 ± 7.35 (m, 3 H); 7.55 ± 7.66 (m, 4 H); 7.80 (d, J ˆ 8.5,
1 H); 7.83 (d, J ˆ 7.9, 1 H); 8.39 (d, J ˆ 8.8, 1 H). 13C-NMR (125 MHz): 39.7 (t); 76.9 (d); 84.0 (d); 123.4 (s);
125.3 (d); 125.8 (d); 126.9 (d); 127.5 (d); 127.7 (d); 127.8 (d); 127.9 (d); 128.1 (d); 128.2 (d); 128.6 (d); 132.2 (s);
‡
‡
135.0 (s); 139.7 (s); 141.5 (s); 164.6 (s). MS: 365 (18, M ), 363 (18, M ), 132 (18), 131 (10), 105 (11), 104 (100),
‡
‡
103 (13), 77 (10). HR-MS: 363.0243 (C20H1479BrNO ; calc. 363.0259), 365.0198 (C20H14 81BrNO ; calc.
365.0238).
Ligand XI. As described for Xb, with 27 (400 mg, 1.10 mmol). The crude product was purified by FC (SiO2,
pentane/AcOEt 95 :5): XI (810 mg, 74%) as a mixture of two diastereoisomers in a 83 :17 ratio. The de of a
small sample could be increased to >98% after HPLC. M.p. 228. [a]2D0 ˆ ‡235.2 (c ˆ 1.02, CHCl3). IR (CHCl3):
3014s, 2968m, 1630s, 1360w, 1224s, 1099m, 998m. 1H-NMR (500 MHz, CDCl3): 2.39 (d, J ˆ 17.7, 2 H); 2.89
(dd, J ˆ 17.7, 7.0, 2 H); 4.63 ± 4.68 (m, 2 H); 5.27 (d, J ˆ 7.9, 2 H); 7.01 ± 7.19 (m, 6 H); 7.40 ± 7.45 (m, 2 H); 7.87
(d, J ˆ 8.2, 2 H); 7.92 (d, J ˆ 8.8, 2 H); 8.00 (d, J ˆ 8.8, 2 H). 13C-NMR (125 MHz): 39.0 (t); 76.3 (d); 82.6 (d);
124.9 (s); 125.3 (d); 125.8 (d); 126.0 (d); 126.3 (d); 126.8 (d); 127.0 (d); 127.1 (d); 127.6 (d); 127.7 (d); 127.8 (d);
‡
133.0 (s); 134.0 (s); 137.5 (s); 139.7 (s); 141.7 (s); 164.5 (s). MS: 569 (20), 568 (47, M ), 411 (35), 410 (100), 307
(15), 306 (63), 294 (11), 278 (15), 277 (16), 116 (16), 115 (38), 104 (16), 103 (13), 55 (21). HR-MS: 568.2145
‡
(C40H28N2O2 ; calc. 568.2151).

Helvetica Chimica Acta ± Vol. 84 (2001)
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2,6-Bis[(4S)-4-(cyclohexylmethyl)-4,5-dihydrooxazol-2-yl]pyridine (XIIc). To 23 (338 mg, 1.74 mmol) and
Et3N (664 ml, 4.8 mmol) in CH2Cl2 (5.0 ml) at 08, pyridine-2,6-dicarbonyl dichloride (28; 162 mg, 0.79 mmol) in
CH2Cl2 was slowly added. The mixture was allowed to stand at r.t. overnight. SOCl2 (578 ml, 7.94 mmol) was
added, and the mixture was heated to reflux for 2 h and then slowly poured on ice. The org. layer was washed
with sat. NaCl soln. and 0.1m K2CO3, the org. layer dried (Na2SO4) and evaporated, and the residue purified by
FC (SiO2, CH2Cl2/MeOH 95 :5): crude 29 as a solid. MeOH (5.5 ml), H2O (2.5 ml), and NaOH (191 mg,
4.76 mmol) were added, and the mixture was heated to reflux for 2 h. After repeated extraction with CH2Cl2, the
org. layer was dried (Na2SO4) and evaporated and the residue recrystallized from hexane/AcOEt: XIIc (224 mg,
69%). M.p. 208 ± 2108. [a]D20
ˆ
134.2 (c ˆ 1.05, CHCl3). IR (CHCl3): 3020s, 2925s, 2853s, 1644s, 1572m, 1476m,
1449m, 1208s, 1046s, 975s, 715s. 1H-NMR (400 MHz, CDCl3): 0.89 ± 1.02 (m, 4 H); 1.09 ± 1.34 (m, 6 H); 1.35 ±
1.43 (m, 2 H); 1.44 ± 1.57 (m, 2 H); 1.59 ± 1.83 (m, 12 H); 4.05 ± 4.11 (m, 2 H); 4.36 ± 4.46 (m, 2 H); 4.59 (dd, J ˆ
8.3, 9.4, 2 H); 7.85 (t, J ˆ 7.8, 1 H); 8.16 (d, J ˆ 7.8, 2 H). 13C-NMR (100 MHz, CDCl3): 26.1 (t); 26.4 (t); 33.3 (t);
‡
33.4 (t); 34.8 (d); 44.1 (t); 64.7 (d); 73.8 (t); 125.5 (d); 137.1 (d); 146.9 (s); 162.0 (s). MS: 409 (100, M ), 408 (16),
367 (13), 313 (32), 312 (61), 286 (11), 285 (43), 284 (32), 283 (21), 272 (13), 271 (14), 270 (27), 269 (13), 259
(11), 258 (51), 257 (13), 256 (55), 245 (10), 244 (45), 243 (25), 242 (64), 228 (14), 214 (20), 174 (13), 162 (10),
161 (10), 160 (18), 148 (12), 147 (20), 146 (24), 145 (35), 138 (30), 136 (11), 131 (17), 130 (13), 124 (18), 122
(10), 121 (18), 119 (11), 118 (17), 117 (28), 106 (16), 105 (16), 104 (15), 103 (23), 95 (13), 93 (15), 91 (10), 90
(13), 81 (39), 79 (21), 78 (14), 77 (14), 67 (33), 56 (17), 55 (94), 54 (11), 53 (13). HR-MS: 409.2692
‡
(C25H35N3O2 ; calc. 409.2729).
2,6-Bis{(4S,5S)-4,5-dihydro-5-(4-nitrophenyl)-4-{[(trialkylsilyl)oxy]methyl}oxazol-2-yl}pyridine (XVb ±
d). Dimethyl Pyridine-2,6-dicarboximidate (31). Pyridine-2,6-dicarbonitrile (30; 1.00 g, 7.74 mmol) and Na
(18 mg, 0.77 mmol) dissolved in MeOH were stirred at r.t. for 36 h. AcOH (44 ml) was added, and the solvent
was evaporated. The solid colorless powder was dried in vacuo: crude 31 (1.48 g, 99%), which was used without
further purification.
2,2'-(Pyridine-2,6-diyl)bis[(4S,5S)-4,5-dihydro-5-(4-nitrophenyl)oxazole-2,4-methanol] (XVa). A suspen-
sion of 31 (1.48 g, 7.66 mmol) and (1S,2S)-2-amino-1-(4-nitrophenyl)propane-1,3-diol (32; 3.58 g, 16.8 mmol,
Aldrich) in (CH2Cl)2 (30 ml) was stirred under reflux during 2 d. After evaporation, MeOH (30 ml) was added
to the residue and the precipitate recovered, washed, and dried: XVa (3.10 g, 78%). Grey amorphous solid. M.p.
2518. [a]2D0 ˆ ‡296.1 (c ˆ 0.31, DMSO). 1H-NMR (500 MHz, (D6)DMSO): 3.62 ± 3.69 (m, 2 H); 3.76 ± 3.83
(m, 2 H); 4.14 ± 4.19 (m, 2 H); 5.17 (t, J ˆ 5.7, 2 H); 5.78 (d, J ˆ 6.6, 2 H); 7.63 (d, J ˆ 8.5, 4 H); 8.14 (dd, J ˆ 7.2,
8.2, 1 H); 8.23 ± 8.30 (m, 6 H). 13C-NMR (125 MHz,(D6)DMSO): 62.7 (t); 77.1 (d); 81.9 (d); 124.0 (d); 126.4 (d);
‡
126.7 (d); 138.4 (d); 146.0 (s); 147.2 (s); 148.4 (s); 161.4 (s). MS: 489 (1, M ), 342 (12), 312 (14), 311 (29), 193
(13), 191 (37), 190 (24), 167 (16), 164 (17), 151 (79), 150 (99), 149 (27), 148 (14), 147 (18), 146 (22), 145 (23),
137 (10), 136 (13), 131 (17), 122 (64), 121 (76), 120 (27), 118 (32), 117 (16), 106 (35), 105 (64), 104 (58), 103
(38), 94 (10), 93 (11), 92 (27), 91 (18), 90 (29), 89 (17), 79 (15), 78 (63), 77 (100), 76 (44), 75 (24), 74 (18), 73
(16), 65 (47), 64 (10), 63 (19), 60 (17), 57 (13), 55 (22), 52 (15), 51 (80), 50 (47). HR-MS: 489.1615
‡
(C25H23N5O6 ; calc. 489.1648).
Ligands XVb ± d: General Procedure. A suspension of XVa (300 mg, 0.58 mmol), tert-butylchlorodi-
methylsilane (191 mg, 1.27 mmol) and 1H-imidazole (208 mg, 3.06 mmol) in DMF (4.0 ml) was stirred overnight
at r.t. The solvent was then evaporated, H2O (10 ml) added, and the mixture extracted with CH2Cl2 (3 Â 30 ml).
The combined org. phase was dried (Na2SO4) and evaporated and the residue purified by FC (SiO2, pentane/
AcOEt 7:3, containing 2% of Et3N): XVb (338 mg, 78%). Colorless foam.
2,6-Bis{(4S,5S)-4-{{[(tert-butyl)dimethylsilyl]oxy}methyl}-4,5-dihydro-5-(4-nitrophenyl)-oxazol-2-yl}pyri-
dine (XVb): [a]2D0 ˆ ‡194.2 (c ˆ 1.09, CHCl3). IR (CHCl3): 3020s, 2954m, 2360m, 1525s, 1348s, 1258m, 1222s,
1110m, 840s. 1H-NMR (500 MHz, CDCl3): 0.10 (s, 6 H); 0.11 (s, 6 H); 0.91 (s, 18 H); 3.75 (dd, J ˆ 8.2, 10.1, 2 H);
4.14 (dd, J ˆ 4.1, 10.1, 2 H); 4.29 ± 4.35 (m, 2 H); 5.78 (d, J ˆ 6.7, 2 H); 7.56 (d, J ˆ 8.5, 4 H); 7.99 (t, J ˆ 7.9, 1 H);
8.21 (d, J ˆ 4.1, 4 H); 8.22 (d, J ˆ 7.0, 2 H). 13C-NMR (125 MHz, CDCl3): 5.4 (q); 5.3 (q); 18.3 (s); 25.8 (q);
‡
65.1 (t); 77.1 (d); 83.8 (d); 123.9 (d); 126.3 (d); 137.6 (d); 146.6 (s); 147.6 (s); 148.0 (s); 162.5 (s). MS: 748 (1, M ),
691 (23), 690 (40), 115 (18), 89 (62), 75 (43), 74 (13), 73 (100), 59 (15), 57 (10), 56 (10). HR-MS: 747.3153
‡
(C37H49N5O8Si2 ; calc. 747.3120).
2,6-Bis{(4S,5S)-4-{{[(tert-butyl)diphenylsilyl]oxy}methyl}-4,5-dihydro-5-(4-nitrophenyl)-oxazol-2-yl}pyri-
dine (XVc). As described above, with (tert-butyl)chlorodiphenylsilane. Yield 84%. [a]2D0 ˆ ‡112.1 (c ˆ 1.00,
CHCl3). IR (CHCl3): 3019s, 2932w, 1525s, 1349s, 1113s, 772s. 1H-NMR (500 MHz, CDCl3): 1.08 (s, 18 H); 3.86
(dd, J ˆ 7.6, 10.4, 2 H); 4.13 (dd, J ˆ 3.8, 10.4, 2 H); 4.32 ± 4.39 (m, 2 H); 5.81 (d, J ˆ 6.3, 2 H); 7.36 ± 7.41
(m, 8 H); 7.42 ± 7.47 (m, 4 H); 7.51 (d, J ˆ 8.8, 4 H); 7.64 ± 7.69 (m, 8 H); 7.95 (t, J ˆ 7.6, 1 H); 8.19 (d, J ˆ 8.5,
4 H); 8.23 (d, J ˆ 7.9, 2 H). 13C-NMR (125 MHz, CDCl3): 19.3 (s); 26.9 (q); 65.6 (t); 77.1 (d); 83.6 (d); 123.9 (d);

1110
Helvetica Chimica Acta ± Vol. 84 (2001)
126.3 (d); 126.4 (d); 127.8 (d); 127.9 (d); 129.9 (d); 130.0 (d); 132.8 (s); 132.9 (s); 135.5 (d); 135.6 (d); 137.5 (d);
‡
146.6 (s); 147.7 (s); 147.9 (s); 162.6 (s). MS: 996 (1, M ), 938 (11), 227 (15), 202 (11), 201 (40), 200 (14), 199
‡
‡
(100), 197 (15), 135 (45), 78 (13), 77 (20). ESI-MS (pos. mode): 996.4 ([M ‡ H] , C57H58N5O8Si2 ; calc. 996.4).
‡
HR-MS: 995.3713 (C57H57N5O8Si2 ; calc. 995.3746).
2,6-Bis{(4S,5S)-4,5-Dihydro-5-(4-nitrophenyl)-4-{[(triisopropylsilyl)oxy]methyl}oxazol-2-yl}pyridine
(XVd). As described above, with chlorotriisopropylsilane. Yield 79%. [a]2D0 ˆ ‡160.0 (c ˆ 1.00, CHCl3). IR
(CHCl3): 3020s, 2945m, 2867m, 1525s, 1348s, 1110m, 754s. 1H-NMR (500 MHz, CDCl3): 1.07 (d, J ˆ 7.2, 18 H);
1.08 (d, J ˆ 7.0, 18 H); 1.12 ± 1.20 (m, 6 H); 3.82 (dd, J ˆ 8.9, 9.5, 2 H); 4.24 (dd, J ˆ 4.1, 10.1, 2 H); 4.32 ± 4.39
(m, 2 H); 5.84 (d, J ˆ 6.3, 2 H); 7.58 (d, J ˆ 8.5, 4 H); 7.99 (t, J ˆ 7.9, 1 H); 8.22 (d, J ˆ 8.5, 4 H); 8.26 (d, J ˆ 7.9,
2 H). 13C-NMR (125 MHz, CDCl3): 11.9 (q); 18.0 (q); 65.6 (t); 77.3 (d); 83.9 (d); 123.9 (d); 126.4 (d); 137.6 (d);
‡
146.7 (s); 147.6 (s); 148.0 (s); 162.6 (s). MS: 832 (1, M ), 292 (25), 276 (26), 274 (25), 235 (85), 233 (100), 210
(43), 196 (46), 167 (64), 153 (34), 127 (21), 126 (58), 67 (21), 57 (31), 55 (73). ESI-MS (pos. mode): 832.4
‡
‡
‡
([M ‡ H] , C43H62N5O8Si2 , calc. 832.4). HR-MS: 832.4088 (C43H61N5O8Si2 ; calc. 831.4059).
REFERENCES
[1] Y. Hayasi, T. Okada, M. Kawanisi, Bull. Chem. Soc. Jpn. 1970, 43, 2506.
[2] L. Hadjiarapoglou, A. Varvoglis, N. W. Alcock, G. A. Pike, J. Chem. Soc., Perkin Trans. 1 1988, 2839; L.
Hadjiarapoglou, S. Spyroudis, A. Varvoglis, J. Am. Chem. Soc. 1985, 107, 7178; L. Hadjiarapoglou,
Tetrahedron Lett. 1987, 28, 4449.
[3] J. N. C. Hood, D. Lloyd, W. A. MacDonald, T. M. Shepherd, Tetrahedron 1982, 38, 3355.
[4] T. Saito, K. Kikuchi, A. Kondo, Synthesis 1995, 87; T. Saito, S. Gon, H. Kikuchi, S. Motoki, J. Chem. Res. (S)
1994, 2; J. Chem. Res. (M) 1994, 223.
[5] B. Karele, O. Neilands, Zh. Org. Chem. 1968, 4, 1818; K. Schank, C. Lick, Synthesis 1983, 392; R. M.
Moriarty, B. R. Bailey, O. Prakash, I. Prakash, J. Am. Chem. Soc. 1985, 107, 1375.
[6] P. Müller, D. Fernandez, Helv. Chim. Acta 1995, 78, 947; P. Müller, D. Fernandez, P. Nury, J.-C. Rossier, J.
Phys. Org. Chem. 1998, 11, 321.
[7] R. M. Moriarty, O. Prakash, R. K. Vaid, L. Zhao, J. Am. Chem. Soc. 1989, 111, 6443; R. M. Moriarty, O.
Prakash, R. K. Vaid, L. Zhao, J. Am. Chem. Soc. 1990, 112, 1297; R. M. Moriarty, J. Kim, L. Guo,
Tetrahedron Lett. 1993, 34, 4129; R. M. Moriarty, E. J. May, O. Prakash, Tetrahedron Lett. 1997, 38, 4333.
Â
[8] P. Müller, C. Bolea, Synlett 2000, 826.
[9] M. P. Doyle, M. N. Protopopova, Tetrahedron 1998, 54, 7919; M. P. Doyle, D. C. Forbes, Chem. Rev. 1998,
98, 911; M. P. Doyle, M. A. McKervey, T. Ye, ꢁModern Catalytic Methods for Organic Synthesis with Diazo
Compoundsꢀ, Wiley, New York, 1997.
Ä
[10] A. M. P. Koskinen, L. Munoz, J. Chem. Soc., Chem. Commun. 1990, 1373; A. M. P. Koskinen, H. Hassila, J.
Ä
Org. Chem. 1993, 58, 4479; A. M. P. Koskinen, L. Munoz, J. Org. Chem. 1993, 58, 879; A. M. P. Koskinen,
H. Hassila, Acta Chem. Scand. 1996, 50, 323.
[11] M. P. Doyle, S. B. Davies, W. Hu, Org. Lett. 2000, 2, 1145.
[12] P. Müller, D. Fernandez, P. Nury, J.-C. Rossier, Helv. Chim. Acta 1999, 82, 935.
Â
[13] C. Bolea, Ph. D. Thesis, University of Geneva, 2001.
[14] K. Kondo, T. Umemoto, Y. Takahatake, D. Tunemoto, Tetrahedron Lett. 1977, 1, 113.
[15] D. F. Taber, J. Am. Chem. Soc. 1977, 99, 3513.
[16] R. M. Moriarty, E. J. May, L. Guo, O. Prakash, Tetrahedron Lett. 1998, 39, 765.
[17] L. Crombie, J. Chem. Soc. 1955, 1007.
[18] R. C. Ronald, J. M. Lansinger, T. S. Lillie, C. J. Wheeler, J. Org. Chem. 1982, 47, 2541.
[19] S. N. Huckin, L. Weiler, J. Am. Chem. Soc. 1974, 96, 1082.
[20] M. Regitz, Angew. Chem., Int. Ed. 1967, 6, 733; M. Regitz, J. Hocker, A. Liedhegener, ꢁOrganic Synthesesꢀ,
Wiley, New York, 1973, Coll. Vol. V, p. 179.
[21] W. Wright, J. Am. Chem. Soc. 1974, 96, 3227; M. M. Jones, J. Am. Chem. Soc. 1959, 81, 3188.
[22] M. G. Moloney, D. R. Paul, R. M. Thompson, E. Wright, Tetrahedron: Asymmetry 1996, 7, 2551.
[23] D. A. Evans, G. S. Peterson, J. S. Johnson, D. M. Barnes, K. R. Campos, K. A. Woerpel, J. Org. Chem. 1998,
63, 4541.
[24] M. B. Andrus, D. Asgari, J. A. Sclafani, J. Org. Chem. 1997, 62, 9365.
[25] E. M. Burgess, H. R. Penton, E. A. Taylor, W. M. Williams, ꢁOrganic Synthesesꢀ, Wiley, New York, 1988,
Coll. Vol. VI, p. 788; E. M. Burgess, H. R. Penton, E. A. Taylor, J. Org. Chem. 1973, 38, 26; E. M. Burgess,
H. R. Penton, E. A. Taylor, J. Am. Chem. Soc. 1970, 92, 5224.

Helvetica Chimica Acta ± Vol. 84 (2001)
1111
[26] T. D. Nelson, A. I. Meyers, J. Org. Chem. 1994, 59, 2655; B. H. Lipshutz, F. Kayser, Z.-P. Liu, Angew.
Chem., Int. Ed. 1994, 33, 1842.
[27] H. Nishiyama, M. Kondo, T. Nakamura, K. Itoh, Organometallics 1991, 10, 500.
[28] G. Desimoni, G. Faita, M. Mella, Tetrahedron 1996, 52, 13649; I. W. Davis, L. Gerena, N. Lu, R. D. Larsen,
P. J. Reider, J. Org. Chem. 1996, 61, 9629; Q.-L. Zhou, A. Pfaltz, Tetrahedron 1994, 50, 4467.
[29] H. Brunner, R. Störiko, F. Rominger, Eur. J. Inorg. Chem. 1998, 771; G. Balavoine, J. C. Clinet, I. Lellouche,
Tetrahedron Lett. 1989, 30, 5141.
[30] M. P. Doyle, W. R. Winchester, M. N. Protopopova, P. Müller, G. Bernardinelli, D. Ene, S. Motallebi, Helv.
Chim. Acta 1993, 76, 2227; P. Müller, P. Nury, Helv. Chim. Acta 2001, 84, in press.
[31] C. V. Patel, M. G. Young, S. P. Robinson, L. Huniban, B. J. Dean, E. M. Gordon, J. Med. Chem. 1996, 39,
4197.
[32] L. McElwee-White, D. A. Dougherty, J. Am. Chem. Soc. 1984, 106, 3466.
[33] K. Burgess, K.-K. Ho, J. Org. Chem. 1992, 57, 5931.
[34] P. Müller, P. Polleux, Helv. Chim. Acta 1994, 77, 645.
[35] R. E. Lowenthal, A. Abiko, S. Masamune, Tetrahedron Lett. 1990, 31, 6005.
[36] D. A. Evans, K. A. Woerpel, M. M. Hinman, M. M. Faul, J. Am. Chem. Soc. 1991, 113, 736.
[37] A. K. Ghosh, P. Mathivanan, J. Cappiello, Tetrahedron Lett. 1996, 37, 3815.
[38] M. P. Sibi, J. J. Shay, M. Liu, C. P. Jasperse, J. Am. Chem. Soc. 1998, 120, 6615.
[39] I. W. Davies, L. Gerena, N. Lu, R. D. Larsen, P. J. Reider, J. Org. Chem. 1996, 61, 9629.
[40] A. Pfaltz, Acc. Chem. Res. 1993, 26, 339; H. Fritschi, U. Leutenegger, G. Umbricht, C. Fahrni, P. von Matt,
A. Pfaltz, Tetrahedron 1992, 48, 2143; D. Müller, G. Umbricht, B. Weber, Helv. Chim. Acta 1991, 74, 232.
[41] K. Mislow, J. Am. Chem. Soc. 1962, 84, 1455.
[42] H. Sawada, H. Hagii, K. Aoshima, M. Yoshida, M. Kobayashi, Bull. Chem. Soc. Jpn. 1985, 58, 3448.
[43] H.-X. Wei, Z.-M. Wang, M. Shi, Chem. Pharm. Bull. 1999, 47, 909.
Received February 9, 2001